Association of anticoagulant therapy with risk of dementia among patients with atrial fibrillation.

AIMS: To investigate the risk of dementia in atrial fibrillation (AF) patients treated with different oral anticoagulants (OACs). METHODS AND RESULTS: This observational, population-based cohort study enrolled 53 236 dementia-free individuals with non-valvular AF who were aged ≥50 years and newly prescribed OACs from 1 January 2013 to 31 December 2016 from the Korean National Health Insurance Service database. Propensity score matching was used to compare the rates of dementia between users of non-vitamin K antagonist oral anticoagulant (NOAC) (dabigatran, rivaroxaban, and apixaban) and warfarin and to compare each individual NOAC with warfarin. Propensity score weighting analyses were also performed. In the study population (41.3% women; mean age: 70.7 years), 2194 had a diagnosis of incident dementia during a mean follow-up of 20.2 months. Relative to propensity-matched warfarin users, NOAC users tended to be at lower risk of dementia [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.90]. When comparing individual NOACs with warfarin, all the three NOACs were associated with lower dementia risk. In pairwise comparisons among NOACs, rivaroxaban was associated with decreased dementia risk, compared with dabigatran (HR 0.83, 95% CI 0.74-0.92). Supplemental propensity-weighted analyses showed consistent protective associations of NOACs with dementia relative to warfarin. The associations were consistent irrespectively of age, sex, stroke, and vascular disease and more prominent in standard dose users of NOAC. CONCLUSION: In this propensity-matched and -weighted analysis using a real-world population-based cohort, use of NOACs was associated with lower dementia risk than use of warfarin among non-valvular AF patients initiating OAC treatment.

In situ procedure for high-efficiency computational modeling of atrial fibrillation reflecting personal anatomy, fiber orientation, fibrosis, and electrophysiology.

We previously reported the feasibility and efficacy of a simulation-guided clinical catheter ablation of atrial fibrillation (AF) in an in-silico AF model. We developed a highly efficient realistic AF model reflecting the patient endocardial voltage and local conduction and tested its clinical feasibility. We acquired > 500 endocardial bipolar electrograms during right atrial pacing at the beginning of the AF ablation procedures. Based on the clinical bipolar electrograms, we generated simulated voltage maps by applying fibrosis and local activation maps adjusted for the fiber orientation. The software's accuracy (CUVIA2.5) was retrospectively tested in 17 patients and feasibility prospectively in 10 during clinical AF ablation. Results: We found excellent correlations between the clinical and simulated voltage maps (R = 0.933, p < 0.001) and clinical and virtual local conduction (R = 0.958, p < 0.001). The proportion of virtual local fibrosis was 15.4, 22.2, and 36.9% in the paroxysmal AF, persistent AF, and post-pulmonary vein isolation (PVI) states, respectively. The reconstructed virtual bipolar electrogram exhibited a relatively good similarities of morphology to the local clinical bipolar electrogram (R = 0.60 ± 0.08, p < 0.001). Feasibility testing revealed an in situ procedural computing time from the clinical data acquisition to wave-dynamics analyses of 48.2 ± 4.9 min. All virtual analyses were successfully achieved during clinical PVI procedures. We developed a highly efficient, realistic, in situ procedural simulation model reflective of individual anatomy, fiber orientation, fibrosis, and electrophysiology that can be applied during AF ablation.

Persistent atrial fibrillation over 3 years is associated with higher recurrence after catheter ablation.

INSTRUCTION: Longer atrial fibrillation (AF) durations have higher recurrence rates after rhythm control. However, there is limited data on the effect of the AF duration on recurrence after atrial fibrillation catheter ablation (AFCA). In the present study, we investigated the rhythm outcome of AFCA according to the AF duration based on the first electrocardiogram (ECG) diagnosis. METHODS AND RESULTS: We included 1005 patients with AF (75% male, 59 ± 11 years old) who underwent AFCA and whose first ECG diagnosis time point was evident. The clinical characteristics and rhythm outcomes were compared based on the AF duration (≤3 years, n = 537; >3 years, n = 468) and AF burden (paroxysmal atrial fibrillation [PAF], n = 387; persistent atrial fibrillation [PeAF], n = 618). Longer AF durations were associated with older age (P = .020), larger left atrial size (P = .009) and a higher number of patients with hypertension (P < .001) or PeAF (P < .001). During 24 ± 22 months of follow-up, the postablation clinical recurrence rate was higher in patients with a longer AF duration (logrank P = .002). The AF recurrence rate was significantly higher in PeAF patients with an AF duration >3 years (logrank P = 0.009), but not in subjects with PAF (logrank P = .939). In a multivariate Cox regression analysis, a longer AF duration was significantly associated with a higher clinical recurrence rate after AFCA in PeAF patients (adjusted hazard ratio, 1.06; range, 1.03-0.10; P = 0.001), but not PAF. CONCLUSION: Although longer AF duration was associated with higher clinical recurrence rates after AFCA, the rate was significant in patients with PeAF lasting >3 years, but not in PAF patients.

Long-term fine particulate matter exposure and cardiovascular mortality in the general population: a nationwide cohort study.

BACKGROUND: Although eastern Asian countries are exposed to high levels of air pollution, the impact of long-term exposures to fine particulate matter (PM2.5) air pollution on all-cause and cardiovascular mortality is not well identified. We assessed the relationship between long-term PM2.5 exposure and all-cause/cardiovascular mortalities. METHODS: We included 436,933 subjects who received national health examinations from the Korean National Health Insurance Service-based National Sample Cohort. We matched subjects' residential-address areas with hourly-measurements of PM2.5 concentration data. We estimated the risk of mortality with average PM2.5 exposure during the study period using a Cox proportional-hazards model. RESULTS: During 1,683,271 person·years, all-cause and cardiovascular mortalities were observed in 6432 and 1603 subjects (382 and 95 per 100,000 person·years, respectively). An increase in 10 µg/m3 in PM2.5 was associated with increases in all-cause and cardiovascular mortalities by 3.4 % [2.7-4.1] and 4.7 % [3.6-5.8], respectively (each p < 0.001). PM2.5 was linearly and significantly correlated with these all-cause and cardiovascular mortalities above 18 µg/m3 of PM2.5 (p < 0.001), but it was not significant below 18 µg/m3 of PM2.5. To investigate the specific PM2.5 concentration for raising cardiovascular mortality more, we analyzed the sensitivities/specificities for different PM2.5 levels, and 18 µg/m3 showed the highest Youden's index (sensitivity + specificity-1) with c-index of 0.85 (0.84-0.86). PM2.5 effect on all-cause mortality was more profound in subjects with previous myocardial infarction compared to the opposite population. CONCLUSIONS: In the Korean general population exposed to high-air pollution, long-term PM2.5 exposure was linearly associated with increased risk for all-cause and cardiovascular mortality, especially above 18 µg/m3 of PM2.5.

The Electrical Isolation of the Left Atrial Posterior Wall in Catheter Ablation of Persistent Atrial Fibrillation.

OBJECTIVES: This study explored whether complete electrical isolation of the left atrial (LA) posterior wall improves the rhythm outcome of catheter ablation of persistent atrial fibrillation (AF). BACKGROUND: Although the STAR AF2 (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) proved no additional benefit of empirical extra-pulmonary vein (PV) LA ablation, the long-term recurrence rate after circumferential PV isolation (CPVI) alone remains high. METHODS: We randomly assigned 217 patients with persistent AF (83.1% men, age 58.7 ± 10.8 years, 73.3% long-standing persistent AF) to ablation with CPVI alone (CPVI group) or CPVI with a POsterior wall Box Isolation (POBI group). The endpoint of the POBI group was the elimination of the posterior atrial potentials by roof and posterior inferior lines and touch-up focal ablation. RESULTS: After a mean follow-up of 16.2 ± 8.8 months, the clinical recurrence rate did not significantly differ between the 2 groups (23.8% vs. 26.5%; p = 0.779) in the CPVI and POBI groups. The recurrence rate for atrial tachycardias (16.0% vs. 11.1%; p = 0.913) and cardioversion rates (6.7% vs. 13.7%; p = 0.093) to control clinical recurrences also did not significantly differ between the 2 groups. At the final follow-up, sinus rhythm was maintained without antiarrhythmic drug in 50.5% and 55.9% in the CPVI and POBI groups, respectively (p = 0.522). No significant difference was found in the major complication rates between the 2 groups, but the total ablation time was significantly longer in the POBI group (4,289 ± 1,837 s vs. 5,365 ± 2,358 s; p < 0.001). CONCLUSIONS: In patients with persistent AF, an empirical complete POBI did not improve the rhythm outcome of catheter ablation or influence the type of recurrent atrial arrhythmia. (Comparison of Circumferential Pulmonary Vein Isolation Alone Versus Linear Ablation in Addition to Circumferential Pulmonary Vein Isolation for Catheter Ablation in Persistent Atrial Fibrillation: Prospective Randomized Controlled Trial; NCT02721121).

Improved Population-Based Clinical Outcomes of Patients with Atrial Fibrillation by Compliance with the Simple ABC (Atrial Fibrillation Better Care) Pathway for Integrated Care Management: A Nationwide Cohort Study.

BACKGROUND: An integrated care approach might be of benefit for clinical outcomes of patients with atrial fibrillation (AF). This study evaluated whether compliance with the Atrial fibrillation Better Care (ABC) pathway for integrated care management ("A" Avoid stroke; "B" Better symptom management; "C" Cardiovascular risk and Comorbidity optimization) would improve population-based clinical outcomes in a nationwide AF cohort. METHODS AND RESULTS: From the Korea National Health Insurance Service database, a total of 204,842 nonvalvular AF patients were enrolled between January 1, 2005 and December 31, 2015. Patients that fulfilled all criteria of the ABC pathway were defined as the "ABC" group, and those who did not were the "Non-ABC" group.Over a mean follow-up of 6.2 ± 3.5 years, the ABC pathway compliant group had lower rates of all-cause death (0.80 vs. 2.72 per 100 person-years, p < 0.001) and the composite outcome of "death, ischemic stroke, major bleeding, and myocardial infarction" (2.34 vs. 5.92 per 100 person-years, p < 0.001) compared with the Non-ABC compliant group. Adjusted Cox multivariable regression showed that the ABC group had a significantly lower risk of all-cause death (adjusted hazard ratio [HR] 0.82; 95% confidence interval [CI], 0.78-0.86) and the composite outcome (adjusted HR 0.86; 95% CI, 0.83-0.89). With the increasing numbers of ABC pathway criteria fulfilled, the risk of all-cause death and composite outcome were progressively lowered. CONCLUSION: In the first study of a nationwide population cohort, we show that compliance with the simple ABC pathway is associated with improved clinically relevant outcomes of patients with AF. Given the high health care burden associated with AF, such a streamlined holistic approach to AF management should be implemented, to improve the care of such patients.

Multiple factors influence the morphology of the bipolar electrogram: An in silico modeling study.

Although bipolar electrograms (Bi-egms) are commonly used for catheter mapping and ablation of cardiac arrhythmias, the accuracy and reproducibility of Bi-egms have not been evaluated. We aimed to clarify the influence of the catheter orientation (CO), catheter contact angle (CA), local conduction velocity (CV), scar size, and catheter type on the Bi-egm morphology using an in silico 3-dimensional realistic model of atrial fibrillation. We constructed a 3-dimensional, realistic, in silico left atrial model with activation wave propagation including bipolar catheter models. Bi-egms were obtained by computing the extracellular potentials from the distal and proximal electrodes. The amplitude and width were measured on virtual Bi-egms obtained under different conditions created by changing the CO according to the wave direction, catheter-atrial wall CA, local CV, size of the non-conductive area, and catheter type. Bipolar voltages were also compared between virtual and clinically acquired Bi-egms. Bi-egm amplitudes were lower for a perpendicular than parallel CO relative to the wave direction (p<0.001), lower for a 90° than 0° CA (p<0.001), and lower for a CV of 0.13m/s than 0.48m/s (p<0.001). Larger sized non-conductive areas were associated with a decreased bipolar amplitude (p<0.001) and increased bipolar width (p<0.001). Among three commercially available catheters (Orion, Pentaray, and Thermocool), those with more narrowly spaced and smaller electrodes produced higher voltages on the virtual Bi-egms (p<0.001). Multiple factors including the CO, CA, CV, and catheter design significantly influence the Bi-egm morphology. Universal voltage cut-off values may not be appropriate for bipolar voltage-guided substrate mapping.

Impact of Renal Function on Outcomes With Edoxaban in Real-World Patients With Atrial Fibrillation.

Background and Purpose- Edoxaban is a direct oral factor Xa inhibitor with proven efficacy and safety among patients with atrial fibrillation. Concerns have been raised about an excess of stroke among patients with creatinine clearance (CrCl) >95 mg/mL treated with edoxaban. We assessed the real-world effectiveness and safety of edoxaban in atrial fibrillation patients in relation to CrCl. Methods- In the Korean National Health Insurance Service data during the period from January to December 2016, we identified 9537 edoxaban-treated patients. Effectiveness and safety outcomes were compared between high-dose edoxaban regimen (HDER, 60 mg daily, n=2840) and a propensity score-matched warfarin group (n=2840) and between low-dose edoxaban regimen (LDER, 30 mg daily, n=3016) and matched warfarin group (n=3016). Results- The median follow-up period was 5.0 months (interquartile range, 2-7 months). The mean age was 68 years, and 63% were men in HDER group, and the mean age was 73 years, and 52% were men in LDER group. Compared with warfarin, both HDER and LDER significantly decreased the risk for ischemic stroke or systemic embolism (S/SE; HDER: adjusted hazard ratio [aHR], 0.44; 95% CI, 0.31-0.64; LDER: aHR, 0.57; 95% CI, 0.42-0.78), major bleeding (HDER: aHR, 0.40; 95% CI, 0.26-0.61; LDER: aHR, 0.61; 95% CI, 0.43-0.85), and mortality (HDER: aHR, 0.34; 95% CI, 0.22-0.53; LDER: aHR, 0.55; 95% CI, 0.41-0.73). In patients with CrCl >95 mL/min, the incidence of S/SE was higher with LDER than warfarin and comparable between HDER and warfarin group. There was lower effectiveness for the prevention of S/SE with LDER compared with warfarin at higher CrCl levels ( P for interaction=0.023). Conclusions- In real-world practice, both doses of edoxaban were associated with reduced risks for S/SE, major bleeding, and mortality compared with warfarin. LDER had lower effectiveness for the prevention of S/SE compared with warfarin at higher levels of CrCl (>95 mL/min).

10-year nationwide trends of the incidence, prevalence, and adverse outcomes of non-valvular atrial fibrillation nationwide health insurance data covering the entire Korean population.

BACKGROUND: Most data on the clinical epidemiology of atrial fibrillation (AF) are reported from Western populations, and data for Asians are limited. We aimed to investigate the 10-year trends of the prevalence and incidence of non-valvular AF and provide prevalence projections till 2060 in Korea. We also investigated the annual risks of adverse outcomes among patients with AF. METHODS: Using the Korean National Health Insurance Service database involving the entire Korean population, a total of 679,416 adults with newly diagnosed AF were identified from 2006 to 2015. The incidence and prevalence of AF and risk of adverse outcomes following AF onset were assessed. RESULTS: The prevalence of AF progressively increased by 2.10-fold from 0.73% in 2006 to 1.53% in 2015. The trend of its incidence was flat with a 10-year overall incidence of 1.77 per 1,000 person-years. The prevalence of AF is expected to reach 5.81% (2,290,591 patients with AF) in 2060. For a decade, the risk of all-cause mortality following AF declined by 30% (adjusted hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.68-0.72), heart failure by 52% (adjusted HR: 0.48, 95% CI: 0.44-0.51), and ischemic stroke by 9% (adjusted HR: 0.91, 95% CI: 0.88-0.93). CONCLUSIONS: The burden of AF among Asian patients is increasing. Although the overall risks of cardiovascular events and death following AF onset have decreased over a decade, the event rates are still high. Optimized management of any associated comorbidities should be part of the holistic management approach for patients with AF.

A stepwise approach to conduit puncture for electrophysiological procedures in patients with Fontan circulation.

Aims: In patients with Fontan circulation, the conduit may be punctured for electrophysiological procedures. We evaluated the feasibility and safety of a stepwise approach to conduit puncture in adults who have undergone Fontan operation. Methods and results: We included 13 consecutive patients with lateral tunnel or extracardiac conduit Fontan circulation [median age (interquartile range), 24.0 (16.0-25.0) years; seven men] who had undergone electrophysiological procedures. We performed a stepwise approach to conduit puncture: 1st, Brockenbrough needle; 2nd, Brockenbrough needle with snare; 3rd, extra-steep Brockenbrough needle with/without snare; 4th radiofrequency transseptal needle with/without snare; 5th, wiring through the puncture; 6th, conduit dilation with angioplasty balloon; 7th, non-compliant or cutting balloon; and 8th, Inoue dilator. In 12 patients, conduit puncture was successful. In two, one, and two patients with a lateral tunnel made of the pericardium or right atrial wall, conduit puncture was performed by steps 1st, 2nd, and 4th, respectively. In one, three, two, and one patient with the Goretex lateral tunnel or extracardiac conduit, conduit puncture was performed by steps 1st, 6th, 7th, and 8th, respectively. Puncture time was significantly longer in patients with Goretex conduits than with pericardial conduits [62.0 (50.0-120.0) and 11.5 (10.0-14.8) min, respectively; P < 0.001]. A snare was necessary in patients with angles ≤ 35° between the conduit wall and vertical line. Conclusion: A stepwise conduit puncture approach is feasible and safe in patients with lateral tunnel and extracardiac conduit Fontan circulation. Goretex conduit puncture was more difficult than pericardial conduit puncture.

Does Additional Electrogram-Guided Ablation After Linear Ablation Reduce Recurrence After Catheter Ablation for Longstanding Persistent Atrial Fibrillation? A Prospective Randomized Study.

BACKGROUND: Although circumferential pulmonary vein isolation (CPVI) catheter ablation may not be sufficient for long-standing persistent atrial fibrillation (L-PeAF), it is not clear which ablation strategy is beneficial in addition to CPVI. We sought to investigate whether additional complex fractionated atrial electrogram (CFAE)-guided ablation improves clinical outcomes in L-PeAF patients who exhibit continuous atrial fibrillation (AF) after CPVI and linear ablation (Line). METHODS AND RESULTS: This study enrolled 137 L-PeAF patients (71.4% male, 61.6±10.9 years old) who underwent radiofrequency catheter ablation. We conducted CPVI+Line based on the Dallas lesion set (posterior box+anterior line) after baseline CFAE mapping in all patients. If AF was defragmented (terminated or changed to atrial tachycardia), the procedure was stopped (AF-Defrag group, n=29). If AF was maintained after CPVI+Line, we mapped the CFAE again and randomly assigned the patient to the CPVI+Line group (n=54) or the additional CFAE ablation group (CPVI+Line+CFAE group, n=54). L-PeAF was defragmented during CPVI+Line in 21.2% of patients (29/137, AF-Defrag group). The mean CFAE cycle length was prolonged (P<0.001), and CFAE area (CFAE cycle length <120 milliseconds) was reduced (P<0.001) after CPVI+Line in the remaining patients. Procedure time was longer in the CPVI+Line+CFAE group than the CPVI+Line group (P=0.023), but procedure-related complication rates did not vary. During 22.3±13.2 months of follow-up, the clinical recurrence rates were 17.2% in the AF-Defrag group, 18.5% in the CPVI+Line group, and 32.1% in the CPVI+Line+CFAE group (log rank, P=0.166). CONCLUSIONS: Although CPVI+Line reduces and localizes CFAE area, additional CFAE ablation after CPVI+Line does not improve the clinical outcomes of catheter ablation in patients with L-PeAF.

Pulmonary vein reconnection predicts good clinical outcome after second catheter ablation for atrial fibrillation.

AIMS: Although electrically reconnected pulmonary veins (PV) are the main mechanism of atrial fibrillation (AF) recurrence, PV isolation (PVI) is well-preserved in certain patients who undergo a repeat procedure. We explored the association between PV reconnection and clinical outcomes after a second ablation. METHODS AND RESULTS: This observational cohort study included 143 patients (79.0% male, 56.1 ± 10.0 years old, 65.0% paroxysmal AF) who underwent a second procedure. Pulmonary vein isolation was well-maintained in 52 patients (PVP- group, 36.4%), although the remaining 91 patients showed PV reconnection (PVP+ group). After confirming PVI, we mapped non-PV triggers and conducted trigger ablation or additional linear ablation at redo-procedures. The proportion of females was higher (P = 0.030), and redo-ablation timing after the de novo procedure was later (P = 0.039) in the PVP- group than in the PVP+ group. Additional linear ablations were more likely to be performed in the PVP- group (90.4 vs. 61.5%, P < 0.001). During the 18.4 ± 10.2 month follow-up after the redo-ablation, the PVP+ group showed a lower clinical recurrence rate than the PVP- group (log-rank P = 0.011). The number of reconnected PVs was independently associated with a lower recurrence of AF after the redo-ablation in the total study population (HR 0.56, 95% CI 0.34-0.95, P = 0.032), particularly for patients with paroxysmal AF (HR 0.41, 95% CI 0.19-0.87, P = 0.021). CONCLUSION: Among patients who underwent redo-AF ablation, those with more PV reconnections showed better clinical outcomes than those with fewer PV reconnections. The mechanism of AF recurrence might be different in patients with lower numbers of PV reconnections during redo-procedures.

Prognosis of high sinus heart rate after catheter ablation for atrial fibrillation.

AIMS: Although atrial fibrillation (AF) catheter ablation increases sinus heart rate (HR), its mechanism and prognosis have not yet been clearly elucidated. We hypothesize that post-AF ablation high sinus HR (PA-HSR) is associated with a better clinical outcome of AF ablation without adverse cardiac effects. METHODS AND RESULTS: We studied 991 AF patients (75% male, 58 ± 11 years old, 70% paroxysmal AF) with HR variability (HRV) at 3 months and 1 year after catheter ablation, and pre- and post-1-year echocardiograms. Post-AF ablation high sinus HR was defined as an average HR greater than 2 SD (≥92 bpm) as measured by 24 h Holter. (1) Average HR increased significantly (P< 0.001), and PA-HSR was observed in 28 patients (2.8%) 3 months after AF ablation. At 1 year after catheter ablation, 21% were taking ß-blockers and 36% maintained an average HR of ≥92 bpm. (2) Post-AF ablation high sinus HR was independently associated with pre-procedural high average HR (OR 1.097; 95% CI 1.029-1.169, P= 0.005), high left atrium (LA) electrogram voltage (OR 3.545; 95% CI 1.183-10.618, P= 0.024), and reduced root mean square of differences between successive NN intervals (rMSSD) at 3 months HRV (OR 0.959; 95% CI 0.919-0.999, P= 0.047). (3) At 1 year echocardiography, size reduction of LA (P= 0.055) or LV (P= 0.372) and the improvement in ejection fraction (P= 0.529) were not significantly different between patients with PA-HSR and those without. (4) Throughout 27 ± 17 months of follow-up, patients with PA-HSR showed significantly lower clinical recurrence than those without (log rank, P= 0.020). CONCLUSION: Post-AF ablation high sinus HR was observed in patients with smaller LA size and higher LA electrogram voltage and significant vagal modulation without adverse cardiac effects. Post-AF ablation high sinus HR was associated with a significantly lower clinical recurrence of AF after catheter ablation.

Challenging Achievement of Bidirectional Block After Linear Ablation Affects the Rhythm Outcome in Patients With Persistent Atrial Fibrillation.

BACKGROUND: It is not clear whether bidirectional block (BDB) of linear ablations reduces atrial fibrillation (AF) recurrence after radiofrequency catheter ablation. We hypothesized that BDB of linear ablation has prognostic significance after radiofrequency catheter ablation for persistent AF. METHODS AND RESULTS: Among 1793 consecutive patients in the Yonsei AF ablation cohort, this observational cohort study included 398 patients with persistent AF (75.6% male; age, 59.8±10.3 years) who underwent catheter ablation with a consistent ablation protocol of the Dallas lesion set: circumferential pulmonary vein isolation; cavotricuspid isthmus ablation (CTI); roof line (RL); posterior-inferior line (PIL); and anterior line (AL). BDB rates of de novo ablation lines were 100% in circumferential pulmonary vein isolation, 100% in CTI, 84.7% in RL, 44.7% in PIL, and 63.6% in AL. During 29.0±18.4 months of follow-up, 31.7% (126/398) of the patients showed clinical recurrence. Left atrial posterior wall (LAPW) isolation (BDBs of RL and PIL) was independently associated with lower clinical AF/atrial tachycardia recurrence (hazard ratio, 0.68; 95% CI, 0.47-0.98; P=0.041; log-rank, P=0.017), whereas BDBs of RL or AL were not (log-rank, P=0.178 for RL; P=0.764 for AL). Among 52 patients who underwent repeat procedures (23.0±16.1 months after de novo procedure), the BDB maintenance rates for CTI, RL, PIL, and AL were 94.2% (49 of 52), 63.5% (33 of 47), 62.1% (18 of 29), and 61.8% (21 of 34), respectively. CONCLUSIONS: Although PIL crosses the esophageal contact area, LAPW isolation is important for better clinical outcome in catheter ablation with a linear ablation strategy for patients with persistent AF.

Low P-wave amplitude (<0.1 mV) in lead I is associated with displaced inter-atrial conduction and clinical recurrence of paroxysmal atrial fibrillation after radiofrequency catheter ablation.

AIMS: We hypothesized that P-wave amplitude in lead I is related to left atrial (LA) remodelling and inter-atrial conduction pattern, and has a predictive value for recurrence after radiofrequency catheter ablation (RFCA) among patients with paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: A total of 525 consecutive patients with PAF (76% male, 56 ± 12 years old) who underwent RFCA were included. We compared pre-procedural sinus rhythm electrocardiograms without antiarrhythmic drug effect with LA volume (CT), LA voltage (NavX), the earliest activation site (EAS) conduction pattern of LA, and clinical recurrence rate. P-wave amplitude in lead I was significantly lower in patients with recurrence than in those that remained in sinus rhythm (P < 0.001) during 21 ± 10-month follow-up. P-wave amplitude in lead I was linearly correlated with LA voltage (ß = 2.52, 95% CI 0.606-4.425, P = 0.010), LA conduction velocity (ß = 1.91, 95% CI 0.941-2.876, P < 0.001), and low septal displacement of EAS (ß = -1.67, 95% CI -2.352 to -0.996, P < 0.001). P-wave amplitudes <0.1 mV in lead I were independently associated with clinical recurrence of AF on multivariate Cox regression analysis (adjusted HR 2.163, 95% CI 1.307-3.581, P = 0.003). The integrated area under the curves was 0.705 (95% CI 0.655-0.755). CONCLUSION: Low P-wave amplitude (<0.1 mV) in lead I is related to LA remodelling and displaced inter-atrial conduction pattern to low septum, and independently predicts clinical recurrence after RFCA in patients with PAF.

Clinical impact of quantitative left atrial vortex flow analysis in patients with atrial fibrillation: a comparison with invasive left atrial voltage mapping.

Recently, left atrial (LA) vortex flow analysis using contrast transesophageal echocardiography (TEE) has been shown to be feasible and has demonstrated significant differences in vortex flow morphology and pulsatility between normal subjects and patients with atrial fibrillation (AF). However, the relationship between LA vortex flow and electrophysiological properties and the clinical significance of LA vortex flow are unknown. The aims of this study were (1) to compare LA vortex flow parameters with LA voltage and (2) to assess the predictive value of LA vortex flow parameters for the recurrence of AF after radiofrequency catheter ablation (RFCA). Thirty-nine patients with symptomatic non-valvular AF underwent contrast TEE before undergoing RFCA for AF. Quantitative LA vortex flow parameters were analyzed by Omega flow (Siemens Medical Solution, Mountain View, CA, USA). The morphology and pulsatility of LA vortex flow were compared with electrophysiologic parameters that were measured invasively. Hemodynamic, electrophysiological, and vortex flow parameters were compared between patients with and without early recurrence of AF after RFCA. Morphologic parameters, including LA vortex depth, length, width, and sphericity index were not associated with LA voltage or hemodynamic parameters. The relative strength (RS), which represents the pulsatility power of LA, was positively correlated with LA voltage (R = 0.53, p = 0.01) and LA appendage flow velocity (R = 0.73, p < 0.001) and negatively correlated with LA volume index (R = -0.56, p < 0.001). Patients with recurrent AF after RFCA showed significantly lower RS (1.7 ± 0.2 vs 1.9 ± 0.4, p = 0.048) and LA voltage (0.9 ± 0.7 vs 1.7 ± 0.8, p = 0.004) than patients without AF recurrence. In the relatively small LA dimension group (LA volume index ≤ 33 ml/m(2)), RS was significantly lower (2.1 ± 0.3 vs 1.7 ± 0.1, p = 0.029) in patients with the recurrent AF. Quantitative LA vortex flow analysis, especially RS, correlated well with LA voltage. Decreased pulsatility strength in the LA was associated with recurrent AF. LA vortex may have incremental value in predicting the recurrence of AF.

Linear ablation in addition to circumferential pulmonary vein isolation (Dallas lesion set) does not improve clinical outcome in patients with paroxysmal atrial fibrillation: a prospective randomized study.

AIMS: Although the concept of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) was derived from maze surgery, it is unclear if linear ablation in addition to circumferential pulmonary vein isolation (CPVI) reduces the recurrence rate in patients with paroxysmal AF. Therefore, we compared clinical outcomes of CPVI with additional linear ablations (Dallas lesion set) and CPVI in a prospective randomized controlled study among patients with paroxysmal AF. METHODS AND RESULTS: This study enrolled 100 paroxysmal AF patients (male 75.0%, 56.4 ± 11.6 years old) who underwent RFCA and were randomly assigned to the CPVI group (n = 50) or the catheter Dallas lesion group (CPVI, posterior box lesion, and anterior linear ablation, n = 50). The catheter Dallas lesion group required longer procedure (190.3 ± 46.3 vs. 161.1 ± 30.3 min, P < 0.001) and ablation times (5345.4 ± 1676.4 vs. 4027.2 ± 878.0 s, P < 0.001) than the CPVI group. Complete bidirectional conduction block rate was 68.0% in the catheter Dallas lesion group and 100% in the CPVI group. Procedure-related complication rates were not significantly different between the catheter Dallas lesion (0%) and CPVI groups (4%, P = 0.157). During the 16.3 ± 4.0 months of follow-up, the clinical recurrence rates were not significantly different between the two groups (16.0% in the catheter Dallas lesion group vs. 12.0% in the CPVI group, P = 0.564), regardless of complete bidirectional conduction block achievement after linear ablation. CONCLUSION: Linear ablation in addition to CPVI (catheter Dallas lesion) did not improve clinical outcomes of RFCA in paroxysmal AF patients and required longer procedure times.

Complex fractionated atrial electrograms related to left atrial wall thickness.

INTRODUCTION: The mechanism of complex fractionated atrial electrogram (CFAE) in patients with atrial fibrillation (AF) remains controversial. This study investigated the relationship between CFAE and left atrial (LA) wall thickness. METHODS AND RESULTS: LA muscular wall thickness (excluding fat) was measured by cardiac computed tomography in 31 patients with AF (12 paroxysmal, 19 persistent) prior to catheter ablation procedures. Measurements were performed at 31 distinct LA locations: 3 at roof, 3 at floor, 9 at anterior wall, 9 at posterior wall, 3 at lateral wall, 3 at septum, and 1 at base of the anterior appendage. The range of LA wall thickness (LAWT) varied widely (average 2.4 ± 0.4 mm, range 1.5-3.1 mm) between patients. In addition, there were significant regional differences in LAWT. Each patient had an average of 7.3 ± 3.5 CFAE sites. The LA wall was thicker at CFAE sites (227 sites, 3.0 ± 1.0 mm) than at non-CFAE sites (734 sites, 2.2 ± 0.9 mm, P < 0.001). In 23 of 31 (74%) patients, the LA wall was thicker at CFAE area than at non-CFAE area. There was no difference in LAWT between sites where CFAE vanished and those where CFAE persisted after pulmonary vein isolation (PVI) among sites with CFAE before PVI. The LAWT > 2.5 mm predicted CFAE with a sensitivity of 70% and a specificity of 70%. CONCLUSION: The LAWT correlates well with CFAE areas, suggesting that one of the mechanisms of CFAE might be related to LAWT.

High left atrial pressures are associated with advanced electroanatomical remodeling of left atrium and independent predictors for clinical recurrence of atrial fibrillation after catheter ablation.

BACKGROUND: The clinical significance of left atrial pressure (LAP) has not yet been clearly elucidated in patients with atrial fibrillation (AF). OBJECTIVE: To explore the effects of elevated LAP on pathophysiology and clinical outcome after radiofrequency catheter ablation in patients with AF. METHODS: We measured LAP during both sinus rhythm (SR) and AF in 454 patients 348 (76.7%) men; mean age 58 ± 11 years; 326(71.8%) paroxysmal AF) who underwent radiofrequency catheter ablation and compared LAP at v wave (LAPpeak) and LAP at y descent (LAPnadir) by using imaging (echocardiography and computed tomography), electrophysiologic mapping (NavX), and clinical data. In 280 (61.7%) patients, pulmonary vein (PV) diastolic flow velocity was measured during SR by transesophageal echocardiography. RESULTS: Patients with LAPpeak(SR) ≥19 mm Hg had greater left atrial (LA) dimension (P < .001), LA volume index (P = .003), and E/Em (mitral annular septal area [peak diastolic velocity]; P = .001) but reduced LA voltage (P < .001) and mitral annular septal area (peak systolic velocity; P = .006) compared with patients with LAPpeak(SR) <19 mm Hg. High LAPpeak(SR) was independently associated with anterior LA volume (linear regression coefficient [B] = 0.381; 95% confidence interval [CI] 0.169-0.593; P < .001) and low LA voltage (B = -0.022; 95% CI -0.030 to -0.013; P < .001). PV diastolic flow velocity (B = 0.161; 95% CI 0.083-0.239; P < .001) and E/Em (B = 0.430; 95% CI 0.096-0.763; P = .012) were independent, noninvasive parameters associated with high LApeak(SR). During 13.1 ± 6.0 months of follow-up, high LAPpeak(SR) was an independent predictor for clinical recurrence of AF (hazard ratio 1.887; 95% CI 1.063-3.350; P = .028). CONCLUSION: Elevated LAP was closely associated with electroanatomical remodeling of the LA and was an independent predictor for recurrence after AF ablation. PV diastolic flow velocity and E/Em can be used as a noninvasive parameter predicting high LAPpeak(SR) in patients with AF.

Synergistic restoring effects of isoproterenol and magnesium on KCNQ1-inhibited bradycardia cell models cultured in microelectrode array.

OBJECTIVES: Bradycardia is caused by loss-of-function mutations in potassium channels that regulate phase 3 repolarization of the cardiac action potential. The purpose of this study is to monitor the effects of potassium channel (KCNQ1) inhibition and to evaluate the effects of isoproterenol (ISO) and MgSO4 in restoring sinus rhythm in atrial cells. METHODS: Microelectrode array was used to analyze conduction velocity, voltage amplitude and cycle length of atrial cells (HL-1). A combination of ISO and MgSO4 was used to restore sinus rhythm in these cells. RESULTS: mRNA expression levels of KCNQ1 (42.2 vs. 100%, p < 0.0001), connexin 43 (29.6 vs. 100%, p = 0.0033), atrial natriuretic peptide (31.0 vs. 100%, p = 0.0030), cardiac actin (38.2 vs. 100%, p < 0.0001) and α-myosin heavy chain (31.2 vs. 100%, p = 0.00254) were significantly lower in the KCNQ1 gene-inhibited group compared to the control group. When treated with MgSO4 (1 mM) and ISO (10 µM), conduction velocity (0.0208 ± 0.0036 vs. 0.0086 ± 0.0014 m/s, p = 0.0004) and voltage amplitude (1,210.78 ± 65.81 vs. 124.1 ± 13.30 µV, p < 0.0001) were higher, and cycle length (431.55 ± 2.05 vs. 1,015.15 ± 4.31 ms, p < 0.0001) was shorter than in the gene-inhibited group. CONCLUSION: Inhibition of sinus rhythm in the bradycardia cell model was recovered by treatment with ISO and MgSO4, demonstrating the potency of combination therapy in the treatment of bradycardia.